This grant will address one of NIOSH's new research priority areas, as well as a traditional research priority: surveillance for the occurrence of disorders of reproduction following exposure to one class of potential reproductive toxicants, the volatile organic solvents. The alkylbenzene solvents, toluene and xylene, are among the most frequently encountered occupational and environmental toxicants. In fact, these solvents are among the key Superfund related contaminants identified by ATSDR and EPA. Of relevance for this study of disorders of reproduction are their reported reproductive and developmental effects in animals and postulated neuroendocrine effects in humans. In particular, the research proposed in this grant will begin to probe the mechanisms by which these solvents might affect reproductive function. It will evaluate the feasibility of using pulsatile secretion of the gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH), as biomarkers of solvent induced endocrine disruption, and it will coordinate with a Superfund project that is designed to develop gender specific physiologically-based pharmacokinetic (PBPK) models for solvent exposed workers. This collaboration provides the investigators with a unique opportunity to assess the effects of controlled exposure to alkylbenzene solvents on the amplitude and frequency of gonadotropin pulses. Previous studies have done only single point measurements, thus potentially failing to observe solvent-induced effects. This study will overcome these limitations by using repeated, frequent blood sampling before, during and after controlled solvent exposure to evaluate the effects of acute toluene and xylene vapor inhalation on LH and FSH pulse amplitude, pulse frequency and mean concentration in men and women with normal reproductive function and in oophorectomized women. The specific aims of this small grant proposal are: 1) to study the effect of the alkylbenzene solvents toluene and xylene on LH and FSH secretion in humans, 2) to explore whether the differences in alkylbenzene pharmacokinetics and hormonal milieux between men and women affect their gonadotropin responses to toluene and xylene exposure, 3) to explore how gonadal feedback modulates the effects of toluene and xylene exposure on gonadotropin secretion in women, and 4) to assess whether exposure to levels of toluene and xylene under the currently allowable limits have subtle, but significant effects on human reproductive endocrine function. Future studies would seek to expand on these preliminary experiments to further elucidate the site(s) and mechanism(s) of action of these solvents on reproductive endocrine function.